肝胆胰外科杂志2026，Vol.38Issue(9)：639-649,11.DOI:10.11952/j.issn.1007-1954.2026.09.006
BMP-7通过调控DNMT3B促进肝癌细胞的侵袭及转移
BMP-7 promotes invasion and metastasis of hepatocellular carcinoma cells by regulating DNMT3B
摘要
Abstract
Objective To analyze the expression of bone morphogenetic protein-7(BMP-7)in hepatocellular carcinoma(HCC)and its association with the prognosis of HCC patients.And to investigate the role of BMP-7 in promoting invasion and metastasis of HCC cells by regulating DNA methyltransferase 3B(DNMT3B)in vitro experiments.Methods Transcriptomic data of 374 HCC patients from the TCGA database were analyzed to evaluate BMP-7 expression in HCC and adjacent tissues,as well as the correlation between BMP-7 and DNMT3B expression.A retrospective analysis was performed on 80 HCC patients who underwent surgical resection in the Affiliate Lianyungang Hospital of Xuzhou Medical University from January 2019 to December 2022.BMP-7 protein expression in HCC and adjacent tissues was compared.Clinicopathological characteristics and survival differences were compared between the BMP-7 high expression group(n=46)and the low expression group(n=34).Human HCC SK-HepG2 and SK-Hep3B cells were cultured in vitro.Cells treated with 0.1 μmol/L LDN-193189(an inhibitor of the BMP-7 signaling pathway)served as the inhibition group,while untreated cells served as the control group.The mRNA and protein expression levels of BMP-7 and DNMT3B in the two groups were detected by RT-qPCR and Western blotting,respectively.Cell proliferation in the two gruops was assessed by 5-ethynyl-2'-deoxyuridine(EDU)and colony formation assays.Cell invasion ability in the two groups was evaluated using the Transwell assay.Cell migration ability in the two groups was evaluated by the wound healing assay.And cell apoptosis rate in the two groups was assessed by flow cytometry.Rescue experiment:DNMT3B overexpression plasmid was overexpressed to verify whether it served as a key downstream effector molecule mediating the malignant phenotype of HCC cells regulated by BMP-7.Results Analysis on TCGA data showed that BMP-7 mRNA expression was significantly higher in HCC tissues than that in adjacent tissues,and BMP-7 mRNA expression was positively correlated with DNMT3B mRNA expression(r=0.33,P<0.001).In the 80 HCC patients from the Affiliate Lianyungang Hospital of Xuzhou Medical University,BMP-7 protein expression scores were significantly higher in HCC tissues than those in adjacent tissues[(6.82±1.95)vs(2.34±1.27),t=14.632,P<0.05].Patients of high BMP-7 expression group had higher Child-Pugh grade and poorer tumor differentiation compared to those of low BMP-7 expression group.Kaplan-Meier survival analysis revealed that the 2-,3-and 4-year overall survival(OS)rates of patients in the high BMP-7 expression group were significantly lower than those in the low BMP-7 expression group(χ2=12.48,P=0.031).Compared with the control group,the inhibition group showed significantly reduced mRNA and protein expression levels of BMP-7 and DNMT3B in both SK-HepG2 and SK-Hep3B cells in vitro experiments(all P<0.05).Additionally,the inhibition group exhibited decreased colony formation,increased apoptosis rate,decreased DNA content in the pre-synthetic phase,and increased DNA content in the synthetic phase,as well as significantly reduced cell invasion and migration abilities.Rescue experiments demonstrated that DNMT3B overexpression significantly reversed the inhibitory effect of LDN-193189 on the invasion ability of SK-HepG2 and SK-Hep3B cells,accompanied by restored DNMT3B protein expression levels(P<0.05).Conclusion Analysis of TCGA and real-word clinical data showed that BMP-7 is highly expressed in HCC and is associated with poor prognosis.Further series of cytological studies indicated that BMP-7 promotes HCC cells proliferation,invasion,and migration by upregulating DNMT3B expression.关键词
肝细胞癌/骨形态发生蛋白-7/DNA甲基转移酶3b/细胞侵袭/细胞转移Key words
hepatocellular carcinoma/bone morphogenetic protein-7/DNA methyltransferase 3B/cell invasion/cell metastasis分类
医药卫生引用本文复制引用
苗苗,葛明树,张隆迪,李婷婷,刘飞,李伟..BMP-7通过调控DNMT3B促进肝癌细胞的侵袭及转移[J].肝胆胰外科杂志,2026,38(9):639-649,11.基金项目
连云港市"521工程"项目(LYG065212024081). （LYG065212024081）
